The present invention relates to a method for non-invasively determining the type of tissue matter or the state of tissue matter in a living body. The present invention allows physicians and diagnosticians to determine the presence of healthy or unhealthy tissue and to determine a proper course of treatment. The method of the present invention is also helpful in allowing medical personnel to monitor the effects of treatments such as chemotherapy and X-ray therapy by measuring attenuation information in the affected organ.
In the medical field, especially in oncology, it is difficult to determine the nature of an internal anomaly in a non-intrusive manner. It is also difficult to detect abnormalities at early stages when treatment is most needed. Physicians often use the so-called "biopsy" method to find the presence of abnormal cells. This method requires finding a group of suspicious cells and obtaining little pieces of tissue containing these cells by inserting a needle into the patient's body. Often, the process has to be repeated several times in order to obtain samples from different suspicious spots. To improve the accuracy of this technique, the needle is often directed into the body under the guidance of an X-ray imaging machine or an ultrasound imaging device. For a patient, this can be a painful process because of its invasive nature. It can also be a dangerous process.
Ultrasound diagnostic methods have been used by physicians and diagnosticians to determine the presence of abnormalities in living human tissue. Existing ultrasound diagnostic methods utilize information obtained from sound signals reflected by the organ or tissue matter under examination.
In existing ultrasound diagnostic methods, there are generally two types of displays for examining reflected signals or echoes. One type of display is known as an A-mode display. In this display, each transmitted pulse triggers the sweep of an oscilloscope. Each pulse and the returning echoes are displayed as vertical deflections on the trace. The sweep is calibrated horizontally in units of distance. Vertically, the sweep shows the magnitude of the reflected signals in units of volts. In an A-mode display, the transducer is kept stationary so that any movement of echoes along the trace will be the result of moving targets.
The second type of display is known as the B-mode display. A B-mode display presents a two-dimensional image of a structure such as an organ of the body. In this case, the transducer is moved with respect to the body while the horizontal deflection of the oscilloscope is made to correspond to the movement of the transducer. The movement may be linear, circular or a combination of the two, but where it is anything other than linear, the sweep must be made to compensate for variations in order to provide a true two-dimensional display of the segment being scanned. The B-mode display system employs reflected signals. The magnitudes of the reflected signals are modulated in the oscilloscope scan through brightness.
Operators using a B-mode system know a normal echographic image of the structure of an organ being examined. If there are growths and/or abnormalities in the organ under examination, then the normal echographic B-scan image is different. So, for operators, it is relatively easy to find abnormalities through echographic B-scan images. There is however a big problem in determining what kind of abnormality, anomaly, tumor or growth is present using only a B-scan image.
According to the theory of the propagation of an acoustic wave, any media has its own acoustic absorption coefficient. Attempts have been made to diagnose the nature of abnormalities within the human body by using a combination of A-mode and B-mode imaging to obtain acoustic propagation information. These attempts have been unsuccessful because the intensity or magnitude of the reflected signals from boundaries of the structure of the tissue under examination depend not only on the acoustic characteristics of the tissue but also on the angle of the incident wave to the reflected surface, roughness of the reflected surface, and the geometry of the reflected surface.
Systems employing acoustic theories have been developed to acoustically determine the nature of tissue within a body. One such system is disclosed in USSR Patent No. 406,531 to Yukhananov. This system uses signals at two frequencies directed toward the surfaces or boundaries being examined to determine the attenuation information through a medium. When the desired attenuation data is determined, it is possible to assess the constituency or composition of the anomaly under investigation. This system is based on certain mathematical derivations and theorems which were identified in a paper entitled "Measurement of Ultrasound Attenuation In Vivo" by I. Yukhananov (Yukov) presented at a seminar of the Academy of Science of the USSR on "Electronic Apparatus in Medicine" in Moscow in 1970, in an article entitled "Substantiation of a Method for Measuring Ultrasonic Absorption in Tissues" by I. Yukov et al. in News of Medical Instrumentation, Moscow, 1971 and in an article appearing in the Proceedings of the Third Oncology Conference of Estonia, Latvia and Lithuania, entitled "A New Method of Ultrasonic Differential Diagnosis of Breast Tumors" by I. Yukov et al. These materials illustrate the generation of attenuation data for analyzing materials under investigation. The two-frequency method discussed in those papers has been extensively used. Such systems as that mentioned in Russian Patent No. 406,531 have had limited success. One of the reasons is that the device disclosed therein is based on only A-mode display information.
It is known that soft tissues frequently contain multiple layers. If the normal tissue or a tumor is homogeneous, then the echo signals can be recorded from the front and rear boundaries. If the normal tissue or tumor are not homogeneous, then there are additional signals from the interfaces of the layers. As is known, different layers can have different types of tissue which means different attenuation data according to the type of tissue. Using only A-mode visualization, it is sometimes very difficult to determine from what part of the investigated normal tissue or from what part of the tumor data is obtained. Moreover, the data is often from several layers, although it looks like it is from only one layer. This happens because the boundaries of the layers in many cases are not parallel and one signal can be overlooked because of its weaknesses. In these cases, the data becomes mixed and could lead to diagnostic mistakes. This is why some prior art techniques require the operator to calculate a lot of layers, which is quite time consuming, in order to ensure that data is being taken from a desired layer and from the proper region of the examining organ.
In addition to the aforementioned Russian patent, U.S. Pat. No. 4,202,215 to Meyer discloses a system for determining attenuation coefficients of tissue. This patent discusses several technical papers on the topic as well as the inadequacies of methods such as that proposed in U.S. Pat. No. 4,057,059 to Hill. The system disclosed in the '215 patent senses when the returning echoes are "white" and then calculates the attenuation coefficient of the tissue segment which causes the return echoes to be "white". As defined by the patentee, "white" means a sonic pressure pulse echo which has a substantially uniform spectrum amplitude at all frequency components of the echo. This system was contrasted with the measurement of peak echo amplitudes at two different frequencies as discussed in the system disclosed in the '049 patent.
U.S. Pat. No. 4,414,850 to Miwa et al. describes a method which is based on the theory and mathematics published by Yukov in 1970 and 1971. The method described in said patent for measuring characteristics of attenuations of domains in an object comprises transmitting ultrasonic waves into the object and receiving ultrasonic waves reflected from the object. The measured characteristics of attenuation of reflected waves is determined using signal intensities. In particular, a plurality of ultrasonic waves having different frequencies are transmitted either simultaneously or alternately to an object and the reflected waves are received from the object. The signal intensities corresponding to the transmission frequencies among the reflected waves are stored and the signal intensity ratio is calculated. The signal intensity ratio indicates the attenuation characteristic. The attenuation coefficient can also be obtained using a time interval from the transmission time to the time of the reflected wave is received. The attenuation slope can be obtained from this attenuation coefficient and the frequency difference between transmitted ultrasonic waves.
In later patents, U.S. Pat. Nos. 4,452,082, 4,509,524, 456,019 and 4,575,799, Miwa et al. disclose a dissatisfaction with the technology in the '850 patent and improvements thereto. In the '799 patent, Miwa et al. admit that, in the previous methods, the assumption that reflected signals are not frequency dependent is wrong. Miwa et al. also admit that their three frequency method is impossible to apply because of "errors due to local fluctuation of the spectrum" and other reasons connected with too many complications needed to get correct information.
It should be noted that the method set out in the '799 patent is impractical. In that method, a plurality of transducers with different frequency bandwidths are used to obtain the normalized power frequency spectrum for the measured data. Practically, this is impossible methodologically and technically, it is complicated.
U.S. Pat. No. 4,676,251 to Bernatets illustrates an improvement to the apparatus disclosed in U.S.S.R. Patent No. 406,531. The Bernatets patent discloses a device for the scanning of media by means of ultrasound echography comprising at least one ultrasonic transducer which is associated with a transmitter stage and with a receiver stage which comprises a conventional first processing circuit and a second processing circuit which is connected parallel thereto and which comprises a series connection of a circuit for automatic gain control as a function of the distance of the echoes, a heterodyne circuit, and n parallel channels, each of which comprises a series connection of a circuit for the correction of diffraction effects, a filter for selecting a narrow frequency band from the pass-band of the transducer, a logarithmic amplifier and a divider whose output is connected to one of the n inputs of a circuit for determining values whose output is connected to the display device provided in the first processing circuit.
As mentioned above, it would be very difficult to use two frequency method only as A-mode image information. Inaccuracies are, in part, due to the fact that soft tissue in the body contains numerous layers. If the tissue contains abnormalities such as a tumor, then on the A-mode display would appear reflections caused by the presence of the tumor. The tumor may in turn contain layers of tissue, or it may be homogeneous (in which case the reflected signals displayed in the A-mode should be such showing only the front and rear boundaries of the tumor). However, if the tumor is not homogeneous, then additional signals will be presented from various layers or interfaces in the tumor itself. As is known, different layers in tissue and tumors means different types of tissue throughout the depth of the ultrasonic examination. These different types of tissues have different attenuation coefficients of ultrasonic energy dependent on tissue type. Thus, the A-mode presentation of reflections from an ultrasonic examination has proven difficult in use and in determining what part of the tissue or tumor is being presented. The situation is further complicated by the fact that the tissue/interface boundaries themselves are not straight lines, but are irregular in shape and by the fact that they may be closely spaced to each other so that data presented in the A-mode may be for more than one interface and could consist of non-objective information. To obtain correct or objective tissue information and accurate attenuation data for diagnostic purposes, the '251 patent has the same difficulties as the aforementioned Russian patent.
U.S. Pat. No. 4,546,772 to Flax measures the attenuation information in a human body through spectrum analyses of reflected signals by using a phase locked loop. This method has all the problems previous discussed. Many people have tried to use spectrum analysis to find attenuation information but have not been successful.
U.S. Pat. No. 4,597,292 to Fujii et al., U.S. Pat. No. 4,644,510 to Fujii and U.S. Pat. No. 4,646,748 to Fujii et al. all measure attenuation information in the human body by using two or more frequencies. Like Miwa et al., Fujii et al. suggest making a plurality of scanning lines to obtain the attenuation information. This is practically very difficult or even impossible because one can not get the same profile several times.